The objective of the proposed work is to study morphological, biochemical and functional changes in human platelets subjected to graded shear stresses for various times, and to examine the combined effects of shear stress and foreign surface interaction. The results will contribute to our understanding of the fluid or engineering mechanics of platelet damage, platelet stimulation, and platelet thrombus formation, and may contribute to knowledge regarding the role of platelets in the development of atherosclerosis. Prior work in this research program has shown that shear stress levels of the order associated with prosthetic abnormal valves and during extracorporeal circulation are sufficent to stimulate release of serotonin and adenine nucleotides, to induce platelet aggregation, and to cause impairment of platelet function as indicated by depressed response to added ADP and decreased post-shear rates of serotonin uptake. Slightly higher stress levels result in platelet lysis. The results are dependent on exposure time, and have been obtained under conditions where shear stress effects are of dominant importance. The proposed work will continue to examine the shear stress effects on human platelets, particularly in whole blood, and will include studies of the effects of agents which interfere with platelet function. Particular attention will be given to shear stress stimulation of platelet alpha-granule release, and the possible relationship of shear stimulation to the development of atherosclerosis in the arterial circulation.